{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T15:20:34Z","timestamp":1788621634824,"version":"build-2803163510"},"reference-count":39,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2022,11,28]],"date-time":"2022-11-28T00:00:00Z","timestamp":1669593600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"JPSP KAKENHI","award":["22K10606"],"award-info":[{"award-number":["22K10606"]}]},{"name":"JPSP KAKENHI","award":["20H03955"],"award-info":[{"award-number":["20H03955"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Cocaine abuse has a negative impact on the immune system. To investigate the adverse effects of binge cocaine administration on lymphoid organs such as thymus and spleen, we examined the effects of repeated intravenous (i.v.) administration of cocaine on rats. Sprague Dawley rats (male, 8 weeks old) received 20 mg\/kg body weight of cocaine hydrochloride per day for 7 or 14 days. In addition to a significant loss in the weight of the spleen, consistent with our previous intraperitoneal (i.p.) injection model of binge cocaine abuse (50 mg\/kg cocaine for 7 days), we also found a significant loss of weight as well as apparent shrinkage of the thymus in the cocaine group. Transcriptome analysis of the thymus revealed increased expressions of genes involved in apoptosis, such as Ifi27 and Traf2, as well as decreased expressions of several genes related to lipid metabolism, such as Cd36, Adipoq, Scd1, and Fabp4, in the thymus of the cocaine group (7 days), suggesting an apoptotic loss of thymic cells as well as alterations in lipid metabolism. Paradoxically, cocaine activates PPAR\u03b3, a key transcriptional factor activating lipid metabolism, although ectopic adipogenesis was scarcely observed in the thymus. Further analysis of rats administered 20 mg\/kg cocaine for 14 days revealed ectopic adipogenesis, which was accompanied with the activation of PPAR\u03b3 as well as increased expression of Adipoq and Fabp4, in the thymus. Taken together, these results indicate that repeated cocaine administration induces thymic involution, which is initiated by the loss of thymic cells through apoptosis and subsequent ectopic adipocyte development.<\/jats:p>","DOI":"10.1371\/journal.pone.0277032","type":"journal-article","created":{"date-parts":[[2022,11,28]],"date-time":"2022-11-28T18:28:26Z","timestamp":1669660106000},"page":"e0277032","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["Thymic involution caused by repeated cocaine administration includes apoptotic cell loss followed by ectopic adipogenesis"],"prefix":"10.1371","volume":"17","author":[{"given":"Kana","family":"Unuma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Homare","family":"Kaga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Funakoshi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moeka","family":"Nomura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4410-6432","authenticated-orcid":true,"given":"Toshihiko","family":"Aki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Uemura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,11,28]]},"reference":[{"issue":"10","key":"pone.0277032.ref001","doi-asserted-by":"crossref","first-page":"eaax1532","DOI":"10.1126\/sciadv.aax1532","article-title":"The treatment of cocaine use disorder","volume":"5","author":"KM Kampman","year":"2019","journal-title":"Sci Adv"},{"key":"pone.0277032.ref002","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.atherosclerosis.2017.03.019","article-title":"Vascular disease in cocaine addiction","volume":"262","author":"K Bachi","year":"2017","journal-title":"Atherosclerosis"},{"issue":"3","key":"pone.0277032.ref003","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1007\/s11481-006-9023-5","article-title":"Drugs of abuse, immune modulation, and AIDS","volume":"1","author":"GA Cabral","year":"2006","journal-title":"J Neuroimmune Pharmacol"},{"issue":"7","key":"pone.0277032.ref004","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/S0192-0561(99)00023-5","article-title":"Cocaine effects on immunocompetent cells: an observation of in vitro cocaine exposure","volume":"21","author":"W Xu","year":"1999","journal-title":"Int J Immunopharmacol"},{"issue":"10","key":"pone.0277032.ref005","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1016\/S0024-3205(97)00601-2","article-title":"Suppression of splenic T lymphocyte proliferation by acute cocaine administration","volume":"61","author":"JR Piccotti","year":"1997","journal-title":"Life Sciences"},{"issue":"10","key":"pone.0277032.ref006","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1016\/S0024-3205(98)00008-3","article-title":"The thymolytic effect of cocaine and monoaminergic drugs in the mouse","volume":"62","author":"S-J Choi","year":"1998","journal-title":"Life Sciences"},{"issue":"6","key":"pone.0277032.ref007","doi-asserted-by":"crossref","first-page":"e0252853","DOI":"10.1371\/journal.pone.0252853","article-title":"Sustained splenic contraction after daily cocaine administration in rats","volume":"16","author":"M Nomura","year":"2021","journal-title":"PLoS One"},{"issue":"6503","key":"pone.0277032.ref008","first-page":"369","article-title":"The function of the thymus and its impact on modern medicine","author":"J. 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